Dental caries is an infectious and transmissible disease that is multifactorial & complex, however, the mutans streptococci (MS) are consistently implicated in the etiology. Therefore, studies on the natural history of dental caries as it relates to MS infection/colonization in children are critical to understanding this disease. The overall goal of our project is to perform a longitudinal study of a disparate population of children, i.e., index children, for MS acquisition; characterize dental caries within this high risk population; and identify critical immunological relationships in order to further our understanding of dental caries etiology and prevention. In the previous funding period, two cohorts defined by age, i.e., 5-6 year and 6- 18 month olds, have been longitudinally followed for colonization of newly erupting teeth as this relates to factors critical in caries development. We have identified a finite number of MS strains (Streptococcus mutans) in this high risk population, which can now be followed over time from initial colonization of the oral cavity and specific teeth to the development of caries. We have demonstrated that individuals in this population have a primary strain (genotype) that remains relatively stable with time. This strain specific stability allows for epidemiological evaluation of infection/colonization with factors such as caries incidence and prevalence, salivary immunity, diet, and other behavioral risk factors. We have also documented information from the children's household family members to evaluate MS genetic diversity, dental caries and behavioral risk factors associated with the index children and will continue this work. In the present application, we propose to connect the two cohorts in age and extend beyond the original age ranges to another important dental developmental milestone (i.e., adolescents, and emergence of permanent 2nd molar teeth) by continuing to follow these children and add an additional older cohort. This proposal will, therefore, continue and build on the important information gained in the first five years and incorporate what has been learned to improve the efficiency of data collection and processing. We have found that repetitive extragenic palindromic-PCR (rep- PCR), and the development of a data entry system vastly improves our ability to carry out the studies thus far. These innovations developed in the current funding period will extend the efficiency and usefulness of data collection and analysis as we continue in this proposed renewal. An interdisciplinary team of dentists, basic scientists, epidemiologists and statisticians that has been involved in this study will improve our understanding of the host-parasite relationship of dental caries in children. The results of these studies will provide key information for the development of strategies to help prevent this infectious disease. The continuation of studies in Uniontown, Alabama, which is located in the Black Belt, will improve oral health in this underserved population. The established community links in this underserved population will be critical for the continuation of this study as well as our understanding of gaps in dental health care in this high risk population.